PROJECT SUMMARY Most U.S. adults (68%) take dietary supplements and there is increasing evidence of drug-supplement interactions (DSIs); our ability to readily identify interactions between dietary supplements with prescription medications is currently very limited. To optimize the safe use of dietary supplements, there remains a critical and unmet need for informatics methods to detect DSIs. Our rationale is that an innovative translational informatics framework to discover potential DSIs from the biomedical literature with subsequent screening using clinical evidence from Electronic Health Records (EHR) will enable a new line of research for targeted DSI validation and will also significantly narrow the range of DSIs that must be further explored. Our long-term goal is to use informatics approaches to enhance DSI clinical research and translate its findings to clinical practice ultimately via clinical decision support systems. The objective of this application is to develop a translational informatics framework to enable the discovery of DSIs by linking scientific evidence from the biomedical literature and clinical evidence from our EHR systems. Towards these objectives, we propose the following specific aims: (1) Compile a comprehensive terminology of dietary supplements using online resources and EHR data; (2) Discover potential DSIs from the biomedical literature; and (3) Evaluate potential DSIs using clinical evidence obtained from EHR data. The successful accomplishment of this project will deliver a novel informatics paradigm and resources for identifying most clinically significant DSI signals and their biological mechanisms. This information is critical to subsequent efforts aimed at improving patient safety and efficacy of therapeutic interventions. The results from this study are imperative in order to achieve the ultimate goal of reducing an individual's risk of potential DSIs.